OP0049 FURTHER CHARACTERIZATION OF CLINICAL AND LABORATORY FEATURES OCCURRING IN VEXAS SYNDROME IN A LARGE-SCALE ANALYSIS OF MULTICENTER CASE-SERIES OF 116 FRENCH PATIENTS

Abstract

BackgroundA new autoinflammatory syndrome related to somatic mutations of UBA1 was recently described and called VEXAS syndrome.ObjectivesTo describe clinical characteristics, laboratory findings and outcomes of VEXAS syndrome.MethodsCase-series. Patients referred to a French multicenter registry between November 2020 and May 2021.116 patients with VEXAS syndrome. Frequency and median of parameters and vital status, from diagnosis to the end of the follow-up.ResultsMain clinical features were skin lesions (83.5%), non-infectious fever (63.6%), weight loss (62%), lung involvement (49.6%), ocular symptoms (38.8%), relapsing chondritis (36.4%), venous thrombosis (34.7%), lymph nodes (33.9%), and arthralgia (27.3%). Hematological disease was present in 58 cases (50%), considered as myelodysplastic syndrome (MDS, n= 58) and monoclonal gammapathy of unknown significance (n=12).UBA1 mutations included p.M41T (44.8%), p.M41V (30.2%), p.M41L (18.1%), and splice mutations (6.9%). After a median follow-up of 3.0 years, 18 patients died (15.5%), from infectious origin (n=9) and MDS progression (n=3). Unsupervised analysis identified 3 clusters: cluster 1 (47%) with mild-to-moderate disease; cluster 2 (16%) with underlying MDS and higher mortality rates; cluster 3 (37%) with constitutional manifestations, higher C-reactive protein levels and less frequent chondritis. Five-year probability of survival was 84.2% in cluster 1, 50.5 % in cluster 2, and 89.6% in cluster 3. UBA1 p.Met41Leu mutation was associated with a better prognosis.ConclusionVEXAS syndrome displays a large spectrum of organ manifestations and shows different clinical and prognostic profiles. It also raises a potential impact of the identified UBA1 mutation.Disclosure of InterestsNone declared.